BACKGROUND:Screening for latent tuberculosis (LTB) before initiating advanced therapy for inflammatory bowel disease (IBD) helps reduce the risk of tuberculosis (TB) development. However, there is limited data on screening practices from TB-endemic regions. AIM:To study the practices of screening for LTB and study the incidence of TB in patients with IBD on biological and small molecule inhibitors. METHODS:This retrospective multicentre study analyzed LTB screening practices in IBD patients starting advanced therapies between 2018 and 2022. We included patients who were initiated on biologics (infliximab, adalimumab, vedolizumab) or small molecule inhibitors (tofacitinib). We assessed compliance with LTB screening methods, including the tuberculin skin test, interferon-gamma release assay (IGRA), chest X-ray, and computed tomography chest, both at initiation and annually. We also evaluated the incidence of active TB and its predictors. RESULTS:Of 378 patients (mean age: 36.9 ± 14.9 years, males: 56.9%), 158 (41.8%) and 216 (57.1%) had ulcerative colitis and Crohn's disease, respectively. Advanced therapy used were anti-tumor necrosis factor in 309 (81.74%), tofacitinib in 41 (10.84%) and vedolizumab in 28 (7.40%). Standard screening and diligent screening strategy was employed in 59% and 33% of patients, respectively. Compliance with tuberculin skin test and IGRA was noted in 261 (69.04%) and 298 (78.83%) patients, respectively. Chest X-Ray and computed tomography chest were performed in 300 (79.36%) and 242 (64.02%), respectively. Annual screening in those on advanced therapy for > 1 year was performed in 27.2% (50/184). Active TB developed in 17 (4.49%); 15 (88.23%) were on anti-tumor necrosis factor. LTB was detected in 40 (10.72%), with most diagnosed on the basis of IGRA (21/40, 52.50%). Among 17 patients who developed active TB, LTB screen was negative in 12 (70.58%). CONCLUSION:Standard screening practices for LTB, prior to starting advanced therapy, remain suboptimal (< 60%) in India despite high TB endemicity.

Background: Transjugular intrahepatic portosystemic shunt (TIPSS) outcomes in patients with moderate-to-severe pre-existing kidney disease (PKD, stages G3a-G4) remain poorly characterized. This study aimed to identify potential predictors of mortality specifically in patients with an eGFR 15-59 mL/min/1.73 m2. Methods: We retrospectively analyzed 68 cirrhosis patients with PKD (eGFR < 60 mL/min/1.73 m2) undergoing a TIPSS between April 2021 and April 2024. Clinical outcomes, renal function changes, and 12-month survival were assessed. Statistical analyses included paired t-tests with false discovery rate adjustment and Kaplan-Meier survival analysis to identify potential predictors of mortality. Results: The cohort (mean age 61.0 ± 8.3 years, 83.8% male, 79.4% with PKD G3a-G3b) showed modest improvement in renal function (creatinine 1.93 to 1.75 mg/dL, p = 0.031), though this biochemical change did not predict survival. Overall mortality was 36.8% (95% CI: 25.4-49.5%) at mean follow-up of 6.7 months. Traditional severity scores (MELD, Child-Turcotte-Pugh) showed no significant association with survival (p > 0.05 for all comparisons). In exploratory analyses, mortality was significantly higher in patients with the following: (1) uncontrolled diabetes before a TIPSS (55.2% vs. 25.9%; RR 2.35, 95% CI: 1.08-5.15, p = 0.032); (2) post-TIPSS infection (70.0% vs. 31.0%; HR 5.44, 95% CI: 1.54-19.23, p = 0.009); and (3) post-procedural cardiac events (85.7% vs. 31.1%; p = 0.005). These associations persisted after false-discovery rate adjustment but require prospective validation given the modest sample size and wide confidence intervals. Conclusions: In this exploratory single-center study of patients with moderate PKD undergoing a TIPSS, we observed associations between mortality and pre-TIPSS poorly controlled diabetes, infections, and cardiac events. These hypothesis-generating findings suggest potential areas for future research. Prospective multi-center studies are needed to validate these associations and determine whether interventions targeting these factors improve outcomes.

BACKGROUND:Fatigue affects 60%-80% of patients with cirrhosis, yet no universally effective pharmacologic therapy exists. Taurine, an amino sulfonic acid with antioxidant and membrane-stabilizing properties, may address metabolic mechanisms underlying fatigue. We hypothesized that L-taurine supplementation would significantly reduce fatigue severity compared to standard care in patients with decompensated cirrhosis. METHODS:This single-center, parallel-arm, open-label randomized controlled trial enrolled adults with decompensated cirrhosis (Child-Turcotte-Pugh score 7-13) and clinically significant fatigue (Fatigue Assessment Scale score >22) at a tertiary care center in South India. Participants were randomized via block randomization to L-taurine (1000 mg/d) plus standard care or standard care alone for 12 weeks. The primary outcome was the change in the Fatigue Assessment Scale score. Analysis of covariance examined treatment-by-anaemia interactions. Effect sizes were calculated using Cohen's d. RESULTS:Of 220 randomized patients, 202 completed the study (standard care: n=100; taurine: n=102). The mean FAS change was -6.83±8.70 (standard care) versus -8.08±7.95 (taurine), with no significant difference (mean difference -1.25; 95% CI: -3.55 to 1.05; p=0.288; Cohen's d=-0.15). However, a significant treatment-by-anemia interaction was observed (p=0.009). In patients without anemia (n=41), taurine produced a large treatment effect (-11.90±4.04 vs. -4.57±9.23; p=0.002; Cohen's d=-1.02), whereas patients with anemia (n=161) showed no benefit (p=0.832). Adverse events occurred in 11.8% of patients treated with taurine, all of which were mild. CONCLUSIONS:L-taurine did not improve fatigue in unselected patients with decompensated cirrhosis. A post hoc subgroup analysis suggested potential benefit in patients without anemia; however, given the open-label design, small subgroup size, post hoc nature of the analysis, and the inherent limitations of unblinded patient-reported outcomes, this finding should be considered hypothesis-generating. A confirmatory, placebo-controlled trial enrolling patients without anemia is warranted (Clinical Trials Registry India number CTRI/2023/06/054455).

Background:Complementary and alternative medicine (CAM)-related hepatotoxicity is a growing global concern. We utilized multi-modal analysis to characterize CAM product safety and identify predictors of severe liver injury. Methods:This retrospective study analyzed 386 CAM products from 91 consecutive patients (mean 4.2 products/patient) presenting with CAM-related adverse events at a tertiary center in South India (2021-2023). Product-level analyses characterize the CAM supply chain while patient-level analyses inform clinical outcome associations. Investigations included ingredient documentation, heavy metal quantification, and GC-MS compound profiling. Results:The mean patient age was 48.2 years (75.8% male). ACLF occurred in 39.6% of all patients (36/91) and 41.9% of those with hepatic adverse events (36/86), with associated mortality of 38.9% (14/36) compared to 10.9% (6/55) in non-ACLF presentations (OR 5.20, P = 0.004). Heavy metals exceeded WHO limits in many products: mercury (34%), cadmium (25%), arsenic (21%), and lead (14%). Cadmium exposure exceeding WHO limits showed a strong association with ACLF (75.9% vs 22.6%, P<0.001, FDR q<0.001). The association with mortality did not reach statistical significance after correction for multiple comparisons (34.5% vs 16.1%, uncorrected P = 0.061, FDR q=0.24). Undeclared pharmaceutical adulteration (at least one adulterant found in 27.7% of products; exposure to at least one adulterated product in 46.2% of patients) and animal-derived content (31.3%) were prevalent. Notably, unlabeled product consumption significantly predicted mortality (P = 0.025). Conclusion:CAM-associated liver injury frequently manifests as ACLF with high mortality, driven by pervasive heavy metal contamination and adulteration. Unlabeled product exposure is a strong mortality predictor, highlighting the urgent need for mandatory product surveillance.

Background and objectives Dengue fever represents a major global health burden with hepatic involvement occurring in up to 90% of hospitalized patients. This study aimed to determine in-hospital mortality predictors, characterize clinical outcomes across graded hepatic injury phenotypes, and validate prognostic scoring systems in hospitalized dengue patients. A primary focus was assessing the impact of pre-existing liver conditions on disease trajectory and survival.Methods A retrospective cohort analysis was conducted on 1,484 patients with laboratory-confirmed dengue infection admitted to a tertiary-care center between 2021 and 2024. Patients were stratified by hepatic status into those with pre-existing chronic liver disease, non-chronic steatotic liver involvement, and no liver involvement. Multivariable logistic regression identified independent mortality predictors, while unsupervised clustering distinguished clinical phenotypes. The performance of physiological and liver-specific prognostic scores was evaluated against clinical outcomes.Results The overall in-hospital mortality rate was 5.1%, with 13.1% requiring intensive care admission. Independent predictors of mortality included severe dengue classification, intensive care unit admission, elevated neutrophil-to-lymphocyte ratio, and hypoalbuminemia, with albumin emerging as the strongest single biomarker for risk prediction. Paradoxically, patients with steatotic liver disease demonstrated improved survival compared to those without pre-existing liver disease, supporting an "obesity paradox" in this tropical infection context, whereas decompensated cirrhosis was associated with markedly adverse outcomes. The Albumin-Bilirubin grade successfully stratified hepatic risk, and the Simplified Acute Physiology Score-3 significantly outperformed the Sequential Organ Failure Assessment for predicting mortality in critically ill patients. Four distinct clinical phenotypes with differential mortality ranging from 3.0% to 100% were identified.Conclusions Hypoalbuminemia serves as a critical, accessible prognostic marker in dengue fever. Pre-existing liver pathology demonstrates divergent impacts on outcomes, with steatotic liver disease potentially conferring survival advantage contrary to traditional metabolic risk assumptions. These findings support the utility of liver-specific scoring systems for acute risk stratification in dengue-endemic regions.

Stereotactic body radiotherapy (SBRT) has emerged as a treatment option for hepatocellular carcinoma (HCC) in patients ineligible for thermal ablation or surgery. However, real-world evidence on how physicians select between locoregional therapies, the stage-specific outcomes of these treatment decisions, and the prognostic determinants that transcend treatment modality remains limited. We aimed to (1) characterize real-world treatment allocation patterns between SBRT and other locoregional therapies (OLT) in patients with cirrhosis and HCC, (2) describe disease control, recurrence, and survival outcomes stratified by Barcelona Clinic Liver Cancer (BCLC) stage, and (3) identify adverse prognostic factors for mortality across the overall cohort. This retrospective, single-centre, descriptive observational study included patients with HCC treated between April 2021 and October 2024. Patients received either SBRT or OLT (n = 42, including radiofrequency or microwave ablation, trans-arterial chemoembolization, or combinations thereof). Disease control was assessed at 90 days using modified RECIST criteria. Outcomes were analysed within BCLC strata, and competing risks analysis was performed for recurrence. Prognostic factors for mortality were assessed using Cox regression and Kaplan–Meier analyses across the entire cohort. Real-world physician choices revealed significant confounding by indication: SBRT was preferentially selected for patients with more advanced disease (BCLC B/C/D: 69.5

Background and Aims:EUS-guided therapy for fundal varices targets the gastric shunt or afferent feeders. In cases with multiple feeders, this may not achieve complete obliteration. We aimed to target the single efferent channel in a patient with multiple feeder vessels. Methods:We describe EUS-guided occlusion of the shunt efferent in a patient with gastric variceal bleed and multiple inflow tracts. The efferent was traced from the left renal vein and targeted with coils and cyanoacrylate glue. Results:Coil plus glue embolization of the shunt efferent achieved complete variceal obliteration. The patient had no further variceal bleeding or decompensation at 6 months. At 1-year follow-up, the patient was asymptomatic; small esophageal varices were noted. Conclusions:EUS-guided coil-assisted retrograde transgastric occlusion is a safe and effective alternative to interventional radiology-guided therapy of gastric varices in cases with multiple afferents or feeder vessels. Development of new esophageal varices is a recognized limitation and should be monitored.

Introduction:Inflammatory biomarkers and immune cell function may provide prognostic value beyond traditional severity scores in hospitalized cirrhosis patients. We aimed to characterize inflammatory and immune profiles to determine their predictive value for ICU admission, infection, and long-term mortality, and to develop novel scoring systems. Patients and methods:This retrospective observational cohort study enrolled 78 hospitalized cirrhosis patients. Comprehensive inflammatory profiling included 12 cytokines (multiplex immunoassay), flow cytometry immune markers, and acute phase reactants (e.g., procalcitonin). Outcome measures included ICU admission, infection, and death within 12-24 months. Multivariable logistic regression was used to identify independent predictors and develop three outcome-specific scoring systems. Results:The cohort had a mean MELD3 of 25.14; 38.5% required ICU admission, and 12-24-month mortality was 43.6%. Independent predictors for infection were procalcitonin (≥0.40 ng/mL), IL-6 (≥84 pg./mL), and creatinine (≥1.35 mg/dL) (AUC 0.74). ICU admission was predicted by hepatic encephalopathy, variceal bleeding, procalcitonin (≥0.40 ng/mL), and IL-6 (≥53.69 pg./mL) (AUC 0.82). Long-term mortality was predicted by ICU admission, hemoglobin (≤11.5 g/dL), EGF (≤2.9 pg./mL), and absolute nucleated cell count (≤3,600/μL) (AUC 0.821). Conclusion:Biomarkers reflecting systemic inflammation (IL-6, procalcitonin), immune paresis (low nucleated cell count), and failed regenerative capacity (low EGF) strongly predicted adverse outcomes. Integrating these markers into the proposed 'Sick Cirrhosis Patient Scores' may improve risk stratification, but these models require rigorous external validation.

Background and Aims: Severe alcohol-associated hepatitis (SAH) can trigger unstable decompensations in cirrhosis patients. They experience high rates of emergency department visits and hospitalization. We evaluated real-world clinical outcomes following palliative-faecal microbiota transplantation (pFMT) compared to best supportive care (BSC) in this critically ill population. Patients and Methods: From July 2021 to April 2024, 28 patients on pFMT were compared with 37 on BSC. Patients on pFMT received nasoduodenal healthy donor stool infusion daily for 5-days. Patients were followed up for portal hypertension-related events, infections, hospitalizations, extrahepatic organ failure and 6- and 12-months survival. 16S rRNA sequencing on stool samples collected at baseline and on follow up were analysed for changes in relative abundance (RA) of bacterial communities. Results: Patients were matched for age, type of decompensation and liver disease severity at enrolment. Twelve-month survival was 64.3% in pFMT versus 51.4% in BSC groups. pFMT dramatically reduced hospital readmissions (mean 0.76 ± 0.76 vs. 2.29 ± 1.27, p < 0.001). Unstable decompensations beyond 3 months occurred in 14.3% of pFMT versus 64.9% of BSC (p < 0.001). Organ failures were lesser with pFMT: acute kidney injury 7.7% versus 93.8% (p < 0.001), hepatic encephalopathy 7.1% versus 68.2% (p < 0.001). Infection burden was significantly lower (53.6% vs. 83.8%, p = 0.008), particularly infections requiring admission (17.4% vs. 66.7%, p < 0.001) with pFMT. Microbiome analysis revealed progressive expansion of Gram-negative genera in BSC, and beneficial Actinobacteria in pFMT-treated patients at 3, 6, and 12 months. Conclusions: Palliative FMT represents a unique disease-modifying intervention in end-stage alcohol-related cirrhosis, preventing organ failure progression, reducing healthcare utilization, and improving survival trajectories.

Background and Aims: Sepsis drives mortality in cirrhosis, yet the gut antimicrobial resistance (AMR) landscape remains unmapped in high-burden settings like India. This study aimed to integrate shotgun metagenomics with deep immunophenotyping to define the gut-immune-resistome axis and correlate specific microbial and genetic signatures with clinical outcomes in decompensated cirrhosis. Methods: We analysed 78 hospitalized patients with cirrhosis using stool shotgun metagenomics, multiplex cytokine arrays, and flow cytometry. The microbiome and resistome (AMR genes) were mapped and correlated with disease severity, immune function (monocyte HLA-DR, neutrophil CD64), and clinical endpoints including mortality. Results: Disease severity was characterized by a "Gram-negative bloom" (Klebsiella) alongside pathogenic Enterococcus expansion and novel markers: Clostridium sp. C5-48 (severe decompensation) and Sutterella (ascites). A specific, dense resistome predicted adverse outcomes; the quinolone-resistance gene QnrB4 correlated with mortality and immune paralysis, while the carbapenemase OXA-833 gene was linked to gastrointestinal bleeding. Notably, the commensal Ligilactobacillus salivarius was associated with systemic inflammatory cytokines. Conclusions: This study reveals a "pathogenic ecosystem" in Indian decompensated cirrhosis where the resistome is intrinsically linked to host immune failure. The identification of specific prognostic markers (QnrB4, OXA-833) and inflammatory associations with L. salivarius challenges generic probiotic use and underscores the urgent need for precision, resistome-targeted therapies.

BackgroundChronic liver disease is characterized by progressive hepatic glutathione depletion and oxidative stress, yet antioxidant therapies have historically shown disappointing clinical efficacy in unselected populations. This therapeutic paradox may reflect inadequate patient stratification and failure to distinguish between acute reversible oxidative injury and chronic persistent inflammation. We hypothesized that glutathione supplementation may preferentially benefit distinct cirrhosis phenotypes with active systemic inflammation.MethodsWe conducted a retrospective cohort study of 466 patients with chronic liver disease who received oral glutathione supplementation (500 mg daily, median 30 days) at a tertiary care center. Primary endpoints were all-cause mortality and change in Model for End-Stage Liver Disease 3.0 (MELD-3) score. We employed conventional statistical methods, survival analysis, multivariable regression, machine learning feature importance, and unsupervised K-means clustering to identify distinct patient phenotypes.ResultsOverall mortality was 10.9% over median 417-day follow-up. At the population level, MELD-3 worsened significantly (mean ΔMELD-3 +2.69, p < 0.001), though 33.5% of patients achieved MELD-3 improvement with low mortality (1.9%). Treatment duration showed no dose-response relationship. Counter-intuitively, patients with higher baseline MELD, bilirubin, INR, and C-reactive protein demonstrated better treatment response. K-means clustering identified four phenotypes, with the “Potential High-Risk Responder” cluster (10.9% of cohort, median MELD-3 27.9) showing highest improvement rate (52.9%) and the only mean MELD-3 improvement (ΔMELD-3–0.85), despite highest mortality (23.5%). An “ideal responder profile” comprising younger patients with alcohol-associated liver disease, elevated baseline MELD, preserved albumin, and elevated inflammatory markers achieved 70.5% improvement rates.ConclusionThese findings demonstrate that glutathione supplementation may preferentially benefits patients with advanced, acutely unstable cirrhosis characterized by active systemic inflammation rather than stable compensated disease, challenging indiscriminate antioxidant use and supporting a precision-medicine approach targeting inflammation-rich, treatment-responsive phenotypes in chronic liver disease.